rs1557217723
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001367916.1(MAGT1):c.127C>T(p.Gln43Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 21)
Consequence
MAGT1
NM_001367916.1 stop_gained
NM_001367916.1 stop_gained
Scores
3
1
1
Clinical Significance
Conservation
PhyloP100: 9.49
Genes affected
MAGT1 (HGNC:28880): (magnesium transporter 1) This gene encodes a ubiquitously expressed magnesium cation transporter protein that localizes to the cell membrane. This protein also associates with N-oligosaccharyl transferase and therefore may have a role in N-glycosylation. Mutations in this gene cause a form of X-linked intellectual disability (XLID). This gene may have multiple in-frame translation initiation sites, one of which would encode a shorter protein with an N-terminus containing a signal peptide at amino acids 1-29. [provided by RefSeq, Jul 2017]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-77875573-G-A is Pathogenic according to our data. Variant chrX-77875573-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 539316.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAGT1 | NM_001367916.1 | c.127C>T | p.Gln43Ter | stop_gained | 2/10 | ENST00000618282.5 | |
MAGT1 | NM_032121.5 | c.223C>T | p.Gln75Ter | stop_gained | 2/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAGT1 | ENST00000618282.5 | c.127C>T | p.Gln43Ter | stop_gained | 2/10 | 1 | NM_001367916.1 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 21
GnomAD3 genomes
?
Cov.:
21
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 21
GnomAD4 genome
?
Cov.:
21
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 10, 2023 | For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Gln75*) in the MAGT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MAGT1 are known to be pathogenic (PMID: 24550228). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with X-linked recessive immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (XMEN) (PMID: 31993868). ClinVar contains an entry for this variant (Variation ID: 539316). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A;A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at